Computation of multiple correspondence analysis, with code in R

The generalization of simple correspondence analysis, for two categorical variables, to multiple correspondence analysis where they may be three or more variables, is not straighforward, both from a mathematical and computational point of view. In this paper we detail the exact computational steps involved in performing a multiple correspondence analysis, including the special aspects of adjusting the principal inertias to correct the percentages of inertia, supplementary points and subset analysis. Furthermore, we give the algorithm for joint correspondence analysis where the cross-tabulations of all unique pairs of variables are analysed jointly. The code in the R language for every step of the computations is given, as well as the results of each computation.

The minimax distortion redundancy in empirical quantizer design

We obtain minimax lower and upper bounds for the expected distortionredundancy of empirically designed vector quantizers. We show that the meansquared distortion of a vector quantizer designed from $n$ i.i.d. datapoints using any design algorithm is at least $\Omega (n^{-1/2})$ awayfrom the optimal distortion for some distribution on a bounded subset of${\cal R}^d$. Together with existing upper bounds this result shows thatthe minimax distortion redundancy for empirical quantizer design, as afunction of the size of the training data, is asymptotically on the orderof $n^{1/2}$. We also derive a new upper bound for the performance of theempirically optimal quantizer.

The economic tragedy of the XXth Century: Growth in Africa

The dismal growth performance of Africa is the worst economic tragedy ofthe XXth century. We document the evolution of per capita GDP for thecontinent as a whole and for subset of countries south of the Saharadesert. We document the worsening of various income inequality indexesand we estimate poverty rates and headcounts. We then analyze some ofthe central robust determinants of economic growth reported bySala-i-Martin, Doppelhofer and Miller (2003) and project the annual growthrates Africa would have enjoyed if these key determinants had taken OECDrather than African values. Expensive investment goods, low levels ofeducation, poor health, adverse geography, closed economies, too muchpublic expenditure and too many military conflicts are seen as keyexplanations of the economic tragedy.

Posterior quadrantic epilepsy surgery: technical variants, surgical anatomy, and case series.

OBJECTIVE: Patients with intractable epilepsy due to extensive lesions involving the posterior quadrant (temporal, parietal, and occipital lobes) form a small subset of epilepsy surgery. This study was done with a view to analyze our experience with this group of patients and to define the changes in the surgical technique over the last 15 years. We also describe the microsurgical technique of the different surgical variants used, along with their functional neuroanatomy. METHODS: In this series there were 13 patients with a median age of 17 years. All patients had extensive presurgical evaluation that provided concordant evidence localizing the lesion and seizure focus to the posterior quadrant. The objective of the surgery was to eliminate the effect of the epileptogenic tissue and preserve motor and sensory functions. RESULTS: During the course of this study period of 15 years, the surgical procedure performed evolved toward incorporating more techniques of disconnection and minimizing resection. Three technical variants were thus utilized in this series, namely, (i) anatomical posterior quadrantectomy (APQ), (ii) functional posterior quadrantectomy (FPQ), and (iii) periinsular posterior quadrantectomy (PIPQ). After a median follow-up period of 6 years, 12/13 patients had Engel's Class I seizure outcome. CONCLUSION: The results of surgery for posterior quadrantic epilepsy have yielded excellent seizure outcomes in 92% of the patients in the series with no mortality or major morbidity. The incorporation of disconnective techniques in multilobar surgery has maintained the excellent results obtained earlier with resective surgery.

Bargaining on networks: An experiment

While markets are often decentralized, in many other cases agents in one role can only negotiate with a proper subset of the agents in the complementary role. There may be proximity issues or restricted communication flows. For example, information may be transmitted only through word-of-mouth, as is often the case for job openings, business opportunities, and confidential transactions. Bargaining can be considered to occur over a network that summarizes the structure of linkages among people. We conduct an alternating-offer bargaining experiment using separate simple networks, which are then joined during the session by an additional link. The results diverge sharply depending on how this connection is made. Payoffs can be systematically affected even for agents who are not connected by the new link. We use a graph-theoretic analysis to show that any two-sided network can be decomposed into simple networks of three types, so that our result can be generalized to more complex bargaining environments. Participants appear to grasp the essential characteristics of the networks and we observe a rather consistently high level of bargaining efficiency.

Plasmacytoid dendritic cells promote immunosuppression in ovarian cancer via ICOS costimulation of Foxp3(+) T-regulatory cells.

Epithelial ovarian cancer (EOC) is the fifth most common cause of cancer death among women. Despite its immunogenicity, effective antitumor responses are limited, due, in part, to the presence of forkhead box protein 3-positive (Foxp3(+)) T regulatory (Treg) cells in the tumor microenvironment. However, the mechanisms that regulate the accumulation and the suppressive function of these Foxp3(+) Treg cells are poorly understood. Here, we found that the majority of Foxp3(+) Treg cells accumulating in the tumor microenvironment of EOCs belong to the subset of Foxp3(+) Treg cells expressing inducible costimulator (ICOS). The expansion and the suppressive function of these cells were strictly dependent on ICOS-L costimulation provided by tumor plasmacytoid dendritic cells (pDC). Accordingly, ICOS(+) Foxp3(+) Treg cells were found to localize in close vicinity of tumor pDCs, and their number directly correlated with the numbers of pDCs in the tumors. Furthermore, pDCs and ICOS(+) Foxp3(+) Treg cells were found to be strong predictors for disease progression in patients with ovarian cancer, with ICOS(+) Treg cell subset being a stronger predictor than total Foxp3(+) Treg cells. These findings suggest an essential role for pDCs and ICOS-L in immunosuppression mediated by ICOS(+) Foxp3(+) Treg cells, leading to tumor progression in ovarian cancer.

Expression of apoptosis and survival genes in human memory T cell populations

RESUME Introduction: Les cellules T mémoires humaines sont classées en trois sous-populations sur la base de l'expression d'un marqueur de surface cellulaire, CD45RA, et du récepteur aux chimiokines, CCR7. Ces sous-populations, nommées cellules mémoires centrales (TcM), mémoires effectrices (TEM) et mémoires effectrices terminales (ITEM), ont des rôles fonctionnels distincts, ainsi que des capacités de prolifération et de régénération différentes. Cependant, la génération de ces différences reste encore mal comprise et on ignore les mécanismes moléculaires impliqués. Matériaux et Méthodes: Des cellules mononucléaires humaines du sang périphérique ont été séparées par cytométrie de flux selon leur expression de CD4, CD8, CD45RA et CCR7 en sous-populations de cellules CD4+ ou CD8+ naïves, TcM, TEM ou ITEM. Dans chacune de ces sous-populations, 14 gènes impliqués dans l'apoptose, la survie ou la capacité proliférative des cellules T ont été quantifiés par RT-PCR en temps réel, relativement à l'expression d'un gène de référence endogène. L'ARN provenant de 450 cellules T a été utilisé par gène et par sous-population. Les gènes analysés (cibles) comprenaient des gènes de survie (BAFF, APRIL, BAFF-R, BCMA, TACI, IL-15Rα, IL-7Rα), des gènes anti-apoptotiques (Bcl-2, BclxL, FLIP), des gènes pro-apoptotiques (Bad, Bax, Fast) et le gène anti-prolifératif, Tob. A l'aide de la méthode comparative delta-delta-CT, le taux d'expression des gènes cibles de chaque sous-population des cellules T mémoires CD4+ et CD8+, à été comparée à leur taux d'expression dans les cellules T naïves CD4+ et CD8+. Résultats: Dans les cellules CD8+, les gènes pro-apoptotiques Bax et Fast étaient surexprimés dans toutes les sous-populations mémoires, tandis que l'expression des facteurs anti-apoptotiques et de survie comme Bcl-2, APRIL et BAFF-R, étaient diminués. Ces deux tendances étaient particulièrement accentuées dans les sous-groupes des cellules mémoires TEM et TTEM. A noter que malgré le fait que leur expression était également diminuée dans les autres cellules mémoires, le facteur de survie IL-7Ra, était sélectivement surexprimé dans la sous-population de cellules TcM et l'expression d'IL-15Ra était sélectivement augmentée dans les TEM. Dans les cellules CD4+, le taux d'expression des gènes analysés était plus variable entre les sujets étudiés que dans les cellules CD8+, ne permettant pas de définir un profil d'expression spécifique. L'expression du gène de survie BAFF par contre, a été significativement augmentée dans toutes les sous-populations mémoire CD4+. Il en va de même pour l'expression d' APRIL et de BAFF-R, bien que dans moindre degré. A remarquer que l'expression du facteur anti-apoptotique Fast a été observée uniquement dans la souspopulation des TTEM. Discussion et Conclusions: Cette étude montre une nette différence entre les cellules CD8+ et CD4+, en ce qui concerne les profils d'expression des gènes impliqués dans la survie et l'apoptose des cellules T mémoires. Ceci pourrait impliquer une régulation cellulaire homéostatique distincte dans ces deux compartiments de cellules T mémoires. Dans les cellules CD8+ l'expression d'un nombre de gènes impliqués dans la survie et la protection de l'apoptose semblerait être diminuée dans les populations TEM et TTEM en comparaison à celle des sous-populations naïves et TEM, tandis que l'expression des gènes pro-apoptotiques semblerait être augmentée. Comme ceci paraît être plus accentué dans les TTEM, cela pourrait indiquer une plus grande disposition à l'apopotose dans les populations CCR7- (effectrices) et une perte de survie parallèlement à l'acquisition de capacités effectrices. Ceci parlerait en faveur d'un modèle de différentiation linéaire dans les cellules CD8+. De plus, l'augmentation sélective de l'expression d'IL-7Ra observée dans le sous-groupe de cellules mémoires TEM, et d'IL-15Ra dans celui des TEM, pourrait indiquer un moyen de sélection pour des réponses immunitaires mémoires à long terme par une réponse distincte à ces cytokines. Dans les cellules CD4+ par contre, aucun profil d'expression n'a pu être déterminé; les résultats suggèrent même une résistance relative à l'apoptose de la part des cellules mémoires. Ceci pourrait favoriser l'existence d'un modèle de différentiation plus flexible avec des possibilités d'interaction multiples. Ainsi, la surexpression sélective de BAFF, APRIL et BAFF-R dans les sous-populations individuelles des cellules mémoires pourrait être un indice de l'interaction de ces sous-groupes avec des cellules B. ABSTRACT Introduction: Based on their surface expression of the CD45 isoform and of the CCR7 chemokine receptor, memory T cells have been divided into the following three subsets: central memory (TAM), effector memory (TEM) and terminal effector memory (ITEM). Distinct functional roles and different proliferative and regenerative capacities have been attributed to each one of these subpopulations. The molecular mechanisms underlying these differences; however, remain poorly understood. Materials and Methods: According to their expression of CD4, CD8, CD45RA and CCR7, human peripheral blood mononuclear cells were sorted by flow-cytometry into CD4+ or CD8+ naïve, TAM, TEM and ITEM subsets. Using real-time PCR, the expression of 14 genes known to be involved in apoptotis, survival or proliferation of T cells was quantified separately in each individual subset, relative to an endogenous reference gene. The RNA equivalent of 450 T cells was used for each gene and subset. The target gene panel included the survival genes BAFF, APRIL, BAFF-R, BCMA, TACI, IL-15Rα and IL-7Rα, the anti-apoptotic genes Bcl2, Bcl-xL and FLIP, the pro-apoptotic genes Bad, Bax and Fast, as well as the antiproliferative gene Tob. Using the comparative CT-method, the expression of the target genes in the three memory T cell subsets of both CD4+ and CD8+ T cell populations was compared to their expression in the naïve T cells. Results: In CD8+ cells, the pro-apoptotic factors Bax and Fast were found to be upregulated in all memory T cell subsets, whereas the survival and anti-apoptotic factors Bcl-2, APRIL and BAFF-R were downregulated. These tendencies were most accentuated in TEM and TTEM subsets. Even though the survival factor IL-7Rα was also downregulated in these subsets, interestingly, it was selectively upregulated in the CD8+ TAM subset. Similarly, IL-15Rαexpression was shown to be selectively upregulated in the CD8+ TEM subset. In CD4+ cells, the expression levels of the analyzed genes showed a greater inter-individual variability than in CD8+ cells, thus suggesting the absence of any particular expression pattern for CD4+ memory T cells. However, the survival factor BAFF was found to be significantly upregulated in all CD4+ memory T cell subsets, as was also the expression of APRIL and BAFF-R, although to a lesser extent. Furthermore, it was noted that the pro-apoptotic gene Fast was only expressed in the TTEM CD4+ subset. Discussion and Conclusions: Genes involved in apoptosis and survival in human memory T cells have been shown to be expressed differently in CD8+ cells as compared to CD4+ cells, suggesting a distinct regulation of cell homeostasis in these two memory T cell compartments. The present study suggests that, in CD8+ T cells, the expression of various survival and antiapoptotic genes is downregulated in TEM and TTEM subsets, while the expression of proapoptotic genes is upregulated in comparison to the naïve and the TAM populations. These characteristics, potentially translating to a greater susceptibility to apoptosis in the CCR7- (effector) memory populations, are accentuated in the TTEM population, suggesting a loss of survival in parallel to the acquisition of effector capacities. This speaks in favour of a linear differentiation model in CD8+ T memory cells. Moreover, the observed selectively increased expression of IL-7Rα in CD8+ TAM cells - as that of IL-15Rα in CD8+ TEM cells -suggest that differential responsiveness to cytokines could confer a selection bias for distinct long-term memory cell responses. Relative to the results for CD8+ T cells, those for CD4+ T cells seem to indicate a certain resistance of the memory subsets to apoptosis, suggesting the possibility of a more flexible differentiation model with multiple checkpoints and potential interaction of CD4+ memory cells with other cells. Thus, the selective upregulation of BAFF, APRIL and BAFF-R in individual memory subsets could imply an interaction of these subsets with B cells.

An enhanced concave program relaxation for choice network revenue management

The network choice revenue management problem models customers as choosing from an offer-set, andthe firm decides the best subset to offer at any given moment to maximize expected revenue. The resultingdynamic program for the firm is intractable and approximated by a deterministic linear programcalled the CDLP which has an exponential number of columns. However, under the choice-set paradigmwhen the segment consideration sets overlap, the CDLP is difficult to solve. Column generation has beenproposed but finding an entering column has been shown to be NP-hard. In this paper, starting with aconcave program formulation based on segment-level consideration sets called SDCP, we add a class ofconstraints called product constraints, that project onto subsets of intersections. In addition we proposea natural direct tightening of the SDCP called ?SDCP, and compare the performance of both methodson the benchmark data sets in the literature. Both the product constraints and the ?SDCP method arevery simple and easy to implement and are applicable to the case of overlapping segment considerationsets. In our computational testing on the benchmark data sets in the literature, SDCP with productconstraints achieves the CDLP value at a fraction of the CPU time taken by column generation and webelieve is a very promising approach for quickly approximating CDLP when segment consideration setsoverlap and the consideration sets themselves are relatively small.

Comparative morphology of the mandibles of female polistine social wasps (Hymenoptera, Vespidae, Polistinae)

Comparative morphology of the mandibles of female polistine social wasps (Hymenoptera, Vespidae, Polistinae). Diversity of mandibular forms in female polistines is explored and compared among 116 species of all polistine genera. Inferences about function are made and discussed based on observed form differences. Mandible length and width measurements are analyzed for a subset of polistine species plus two vespines and two eumenines. A variable expressing the ratio between these variables is also considered in morphometric analyses. The following mechanical interactions among mandible structural elements are highlighted: opposition and crossing of mandibles' apical teeth at the middle of the closing trajectory; shearing action of the apical teeth against mesial denticles of the opposite mandible; shearing action of the mandible anterior margin against the ventral margin of the clypeus. In the genera Agelaia and Angiopolybia, exceptionally developed mesial mandibular structures may be related to necrophagy. In some epiponine genera, poorly developed mesial denticles and strong torsion of mandibles may be partially related to use of short wood fibers in nest construction as advanced by Sarmiento (2004). The considerable morphological variation found across the subfamily Polistinae is certain to be important in taxonomic and phylogenetic studies at the genus and species levels.

c-Myc acts downstream of IL-15 in the regulation of memory CD8 T-cell homeostasis.

A subset of CD8 T cells in normal mice, expressing high levels of activation markers such as CD44, shares many properties with antigen-specific memory CD8 T cells. Homeostasis of CD44(high) CD8 T cells depends upon cytokines such as interleukin-15 (IL-15); however, the downstream signaling pathways regulating IL-15-dependent homeostatic proliferation are poorly defined. Surprisingly, we show here that haploinsufficiency of the protooncogene c-myc leads to a highly selective decrease in CD44(high) CD8 T cells in mice. Although steady-state proliferation and survival of CD44(high) CD8 T cells appeared not to be dependent on c-Myc, homeostatic proliferation of c-myc(+/-) CD44(high) CD8 T cells in lymphopenic hosts was strongly reduced, and the residual homeostatic proliferation of these cells appeared to occur independently of IL-15. Moreover, c-myc(+/-) CD44(high) CD8 T cells responded very poorly to purified IL-15 in vitro. Backcrossing of c-myc(+/-) mice to IL-15(-/-) mice revealed that the number of CD44(high) CD8 T cells decreased in an additive fashion in mice heterozygous for c-myc and IL-15. Finally homeostatic proliferation of antigen-specific memory CD44(high) CD8 T cells was also impaired in c-myc(+/-) mice. Collectively, our data identify c-Myc as a novel downstream component of the IL-15-dependent pathway controlling homeostatic proliferation of memory CD44(high) CD8 T cells.

Pre-analytical and methodological challenges in red blood cell microparticle proteomics.

Microparticles are phospholipid vesicles shed mostly in biological fluids, such as blood or urine, by various types of cells, such as red blood cells (RBCs), platelets, lymphocytes, endothelial cells. These microparticles contain a subset of the proteome of their parent cell, and their ready availability in biological fluid has raised strong interest in their study, as they might be markers of cell damage. However, their small size as well as their particular physico-chemical properties makes them hard to detect, size, count and study by proteome analysis. In this review, we report the pre-analytical and methodological caveats that we have faced in our own research about red blood cell microparticles in the context of transfusion science, as well as examples from the literature on the proteomics of various kinds of microparticles.

Exon-primed intron-crossing (EPIC) markers as a tool for ant phylogeography

Exon-primed intron-crossing (EPIC) markers as a tool for ant phylogeography. Due to their local abundance, diversity of adaptations and worldwide distribution, ants are a classic example of adaptive radiation. Despite this evolutionary and ecological importance, phylogeographical studies on ants have relied largely on mitochondrial markers. In this study we design and test exon-primed intron-crossing (EPIC) markers, which can be widely used to uncover ant intraspecific variation. Candidate markers were obtained through screening the available ant genomes for unlinked conserved exonic regions interspersed with introns. A subset of 15 markers was tested in vitro and showed successful amplification in several phylogenetically distant ant species. These markers represent an important step forward in ant phylogeography and population genetics, allowing for more extensive characterization of variation in ant nuclear DNA without the need to develop species-specific markers.

A critical review of the molecular pathophysiology of lenalidomide sensitivity in 5q - myelodysplastic syndromes.

Abstract The 5q deletion is a chromosomal abnormality that is observed in a subset of myelodysplastic syndromes (MDS). When isolated, this abnormality defines a specific clinical syndrome termed MDS associated with isolated deletion 5q, presenting with macrocytic anemia, normal platelet count or slight thrombocytosis, hypolobated megakaryocytes and fewer than 5% blasts in the bone marrow. MDS with the 5q deletion have a particular sensitivity to treatment with lenalidomide, a thalidomide analog. In this article, molecular changes in 5q- MDS derived from haploinsufficiency of genes encoded from the deleted region in 5q are reviewed, and mechanisms that link these molecular lesions with lenalidomide sensitivity are proposed.

Lung microbiota promotes tolerance to allergens in neonates via PD-L1.

Epidemiological data point toward a critical period in early life during which environmental cues can set an individual on a trajectory toward respiratory health or disease. The neonatal immune system matures during this period, although little is known about the signals that lead to its maturation. Here we report that the formation of the lung microbiota is a key parameter in this process. Immediately following birth, neonatal mice were prone to develop exaggerated airway eosinophilia, release type 2 helper T cell cytokines and exhibit airway hyper-responsiveness following exposure to house dust mite allergens, even though their lungs harbored high numbers of natural CD4(+)Foxp3(+)CD25(+)Helios(+) regulatory T (Treg) cells. During the first 2 weeks after birth, the bacterial load in the lungs increased, and representation of the bacterial phyla shifts from a predominance of Gammaproteobacteria and Firmicutes towards Bacteroidetes. The changes in the microbiota were associated with decreased aeroallergen responsiveness and the emergence of a Helios(-) Treg cell subset that required interaction with programmed death ligand 1 (PD-L1) for development. Absence of microbial colonization(10) or blockade of PD-L1 during the first 2 weeks postpartum maintained exaggerated responsiveness to allergens through to adulthood. Adoptive transfer of Treg cells from adult mice to neonates before aeroallergen exposure ameliorated disease. Thus, formation of the airway microbiota induces regulatory cells early in life, which, when dysregulated, can lead to sustained susceptibility to allergic airway inflammation in adulthood.

Substance P-like-immunoreactive sensory neurons in dorsal root ganglia of the chick embryo: ontogenesis and influence of peripheral targets.

The expression of substance P (SP) was studied in sensory neurons of developing chick lumbosacral dorsal root ganglia (DRG) by using a mixture of periodic acid, lysine and paraformaldehyde as fixative and a monoclonal antibody for SP-like immunostaining. The first SP-like-immunoreactive DRG cells appeared first at E5, then rapidly increased in number to reach a peak (88% of ganglion cells) at E8, and finally declined (59% at E12, 51% after hatching). The fall of the SP-like-positive DRG cells resulted from two concomitant events affecting a subset of small B-neurons: a loss of neuronal SP-like immunoreactivity and cell death. After one hindlimb resection at an early (E6) or late (E12) stage of development (that is before or after establishment of peripheral connections), the DRG were examined 6 days later. In both cases, a drastic neuronal death occurred in the ispilateral DRG. However, the resection at E6 did not change the percentage of SP-like-positive neurons, while the resection at E12 severely reduced the proportion of SP-like-immunoreactive DRG cells (25%). In conclusion, connections established between DRG and peripheral target tissues not only promote the survival of sensory neurons, but also control the maintenance of SP-like-expression. Factors issued from innervated targets such as NGF would support the survival of SP-expressing DRG cells and enhance their SP content while other factors present in skeletal muscle or skin would hinder SP expression and therefore lower SP levels in a subset of primary sensory neurons.